New and Potent Quinuclidine-Based Antimicrobial Agents.
Molecules
; 24(14)2019 Jul 23.
Article
en En
| MEDLINE
| ID: mdl-31340589
ABSTRACT
Developing new antibiotics is currently very important since antibiotic resistance is one of the biggest problems of global health today. In the search for a new class of potential antimicrobial agents, ten new compounds were designed and synthesized based on the quinuclidinium heterocyclic core and the oxime functional group. The antimicrobial activity was assessed against a panel of representative gram-positive and gram-negative bacteria. All compounds demonstrated potent activity against the tested microorganisms, with the minimum inhibitory concentration (MIC) values ranging from 0.25 to 256.00 µg/mL. Among the tested compounds, two quaternary compounds, para-N-chlorobenzyl and meta-N-bromobenzyl quinuclidinium oximes, displayed the most potent and broad-spectrum activity against both gram-positive and gram-negative bacterial strains (MIC values from 0.25 to 4.00 µg/mL), with the lowest value for the important multidrug resistant gram-negative pathogen Pseudomonas aeruginosa. In the case of Klebsiella pneumoniae, activity of those compounds are 256-fold and 16-fold better than gentamicin, respectively. MTT assays showed that compounds are nontoxic for human cell lines. Multi-way analysis was used to separately reduce dimensionality of quantum chemical data and biological activity data to obtain a regression model and the required parameters for the enhancement of biological activity.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Oximas
/
Quinuclidinas
/
Diseño de Fármacos
/
Antibacterianos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Año:
2019
Tipo del documento:
Article